title: Molecular biomarkers of resistance to anti-EGFR treatment in metastatic colorectal cancer, from classical to innovation.
abstract: BACKGROUND
  Systematic dissection of the EGFR pathway was considered as the best way to identify putative markers of resistance to anti-EGFR therapies. This kind of approach leaves other, less known but by no means less important, putative mechanisms of resistance. We tried to shed some light on these mechanisms of resistance.
  
  
  METHODS
  We performed a research through Pubmed database of all published articles highlighting mechanisms of resistance to Cetuximab and Panitumumab based therapies, published in 2000-2012 period.
  
  
  CONCLUSIONS
  We reviewed the "classical" molecular factors, extensively analyzed as predictive factors for efficacy to anti-EGFR therapy, such as K-ras, B-raf, and PI3K-mTOR-Akt, focusing on their predictive or prognostic value and on the controversial aspects of the biomarker analysis for clinical practice. On the second part we will then move on to other less known molecular markers, for the future understanding of biological mechanisms underlying anti-EGFR therapy resistance, such as non-canonical heterodimer candidates, microRNA, IGF1-IGF1R, HGF-cMET and secondary mutations of EGFR.
authors.affiliation: Clinica di Oncologia Medica, AOU "Ospedali Riuniti" - Università Politecnica delle Marche, via Conca 71, Torrette, 60020 Ancona, Italy. Electronic address: kakeru@libero.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Michela
authors.initials: M
authors.lastname: Del Prete
authors.forename: Elena
authors.initials: E
authors.lastname: Maccaroni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bittoni
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.forename: Maristella
authors.initials: M
authors.lastname: Bianconi
authors.forename: Luca
authors.initials: L
authors.lastname: Cecchini
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Anti-EGFR; Biomarkers; Colorectal cancer; Resistance